Modern Perspectives in Advanced Melanoma - Episode 2
Evan J. Lipson, MD: The MSLT-II data have been practice changing for multidisciplinary teams, surgery in particular. It used to be that patients with a positive sentinel lymph node in the setting of melanoma would almost invariably go on to a completion lymph node dissection, or at least completion lymph node dissection was the standard of care. The results from the MSLT-II study, of course, demonstrated that there was not an overall survival benefit to doing that. The practice with patients now is that those with a positive sentinel node are oftentimes done with surgery unless there’s a compelling reason to continue with a lymphadenectomy. Those patients, after a positive sentinel node has been found, are oftentimes transferred over to the care of a medical oncologist for the consideration of adjuvant medical therapy.
Brian Gastman, MD: MSLT-II and the ECOG study are in an area of strong interest to me, not just because I am a surgeon but because I do new therapy clinical trials. I’m also interested in the studies’ ramifications. To go back a bit, part of what happened was timing. MSLT-II reported out within around 12 months of KEYNOTE-054, CheckMate 238, and COMBI-AD, which were all the adjuvant trials.
Here is the problem: MSLT-II shows that completion lymphadenectomy after a positive sentinel node—we’re talking about microscopic metastatic disease by definition—did not improve survival. It did improve local-regional relapse-free survival, and that might have ramifications. In that trial, nobody had access to the modern immunotherapies, not even the modern anti-CTLA4 therapies.
Fast-forward to when all those trials were read out, within 12 months. They all required, for those patients with the same scenario, completion lymphadenectomy, so neither trial intersected completely. MSLT-II didn’t have the benefit of the adjuvant therapies, but it said, “Don’t do completion lymphadenectomy.” The 3 major adjuvant trials required completion lymphadenectomy, and most people in their minds have just decided that they will give up completion lymphadenectomy.
If you look at MSLT-II carefully, you will see that there was 1 subset of patients who were head and neck melanoma patients. It is probably because they were understudies, but they were almost better off if they had a neck dissection, not to mention the fact that, when patients recur in the neck, it might be a much worse situation than if they recur elsewhere. They can injure cranial nerves and create long-term permanent functional disabilities as well as cosmetic, aesthetic, and psychosocial problems related to deformity.
The question then is this: For head and neck patients, especially because all the adjuvant data assume they had a neck dissection, we will offer some a neck dissection. We will certainly look at how much tumor burden was in the sentinel node and will make that decision. There is a trial that is percolating now in a cooperative group that may eventually get approved; we will see. We are trying to answer some of these questions, but that is pending as we speak.
For the most part, because we have so much good salvage therapy, we can still operate on the patients later, including anybody below the clavicles with a positive sentinel node regardless of how much disease was present. In fact, in MLST-II, the more disease you had in the lymph node, the less likely lymphadenectomy had any difference, and that’s likely because the cat was already out of the bag: It’s probably really stage IV disease.
We won’t do completion lymphadenectomies unless the patient was absolutely adamant about it. Above the clavicles, I would say maybe one-third of my patients will go on to get a completion lymphadenectomy because of MSLT-II and because of the ramifications of going back and salvaging the situation, if it is even salvageable, with neck dissections, parotidectomy, and so on. You are now dealing with much larger disease.
Transcript Edited for Clarity